Joshua P. Metlay, MD, PhD is the candidate for a Mid-Career Investigator Award in Patient Oriented Research. Dr. Metlay is an Associate Professor of Medicine and Epidemiology at the University of Pennsylvania School of Medicine. Dr. Metlay has devoted the initial portion of his career as a physician scientist to both establishing a nationally recognized program of patient-oriented research in the transmission of pneumococcal disease and management of respiratory tract infections and also establishing a track record of teaching and mentoring focused on creating the next generation of clinical investigators. In terms of clinical research, Dr. Metlay's immediate goals are to further develop his own training in geographic information systems and spatial analyses in order to expand his current work examining neighborhood level determinants of pneumococcal disease spread. Currently funded work in this area includes the grant 5R01- AI046645, "Risk factors for drug resistant pneumococcal bacteremia". This 48 hospital population-based study of pneumococcal bacteremia incorporates geospatial analyses into multivelel models examining the interaction between individual and environmental risk factors in promoting the spread of macrolide resistant pneumococcal disease. As part of this proposal, the candidate will expand this research to examine the individual and neighborhood-level determinants of patterns of carriage of S. pneumoniae among children. The applicant's research team, including microbiologists, epidemiologists, geographers, and statisticians will partner with investigators in pediatrics and an established large primary care research network coordinated at the Children's Hospital of Philadelphia to measure and analyze patterns of pneumococcal carriage among children. Analyses will explore changing patterns in pneumococcal carriage under vaccine pressure and examine individual and neighborhood-level covariates associated with the patterns of pneumococcal carriage. This work will provide a fundamental base for examining the relationship between carriage and invasive disease, particularly in terms of the geographic determinants of pneumococcal disease. In parallel, Dr. Metlay will expand his role as a mentor for future physician scientists interested in careers in patient-oriented research, particularly in the area of acute infectious diseases of the respiratory tract. Through his central roles in the Masters of Science of Clinical Epidemiology and his co-directorship of the Robert Wood Johnson Clinical Scholars program, Dr. Metlay will be in a key position to recruit and direct the training of a substantial number of future clinical investigators. Support from this award will assure his ability to serve as a mentor for a number of these future clinical investigators, particularly in the area of infectious diseases epidemiology.